The effects of isofagomine, a potent glycogen phosphorylase inhibitor, on glycogen metabolism in cultured mouse cortical astrocytes

A novel inhibitor of liver glycogen phosphorylase, isofagomine, was investi gated as a possible inhibitor of the enzyme in the brain and in cultured as trocytes. Additionally, the effect of the drug on norepinephrine (NE) induc ed glycogen degradation in astrocytes was studied. Astrocytes were cultured from mouse cerebral cortex and homogenates were prepared from the cells as well as from mouse brain. Isofagomine dose-dependently inhibited glycogen phosphorylase when measured in the direction of glycogen degradation in bot h preparations with IC50 values (mean +/- SEM) of 1.0 +/- 0.1 mu M and 3.3 +/- 0.5 mu M in brain and astrocyte homogenates, respectively. Moreover, is ofagomine at a concentration of 400 mu M completely prevented NE induced de pletion of glycogen stores and the concomitant lactate production in intact astrocytes. It is suggested that this novel glycogen phosphorylase inhibit or may be a valuable tool to investigate the functional importance of glyco gen in astrocytes and in the brain. (C) 2000 Elsevier Science Ltd. All righ ts reserved.